Evaluation of Tirzepatide As an Adjunct to Buprenorphine for the Treatment of Opioid Use Disorder (TAB)

T. John Winhusen, PhD

Status and phase: Begins enrollment in 3 months; Phase 2

Conditions: Opioid Use Disorder; Opioid Use Disorder, Moderate; Opioid Use Disorder, Severe

Treatments: Drug: Tirzepatide; Other: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06651177

UG1DA013732 (U.S. NIH Grant/Contract)

2024-1003

Details and patient eligibility

About

The primary objective of this research study is to evaluate the effect of tirzepatide, relative to placebo, as an adjunct to BUP on retention, substance use, and sleep outcomes in individuals with OUD.

Full description

This is a Phase 2, pragmatic, multi-site, double-blind, randomized, placebo-controlled, intent-to-treat trial. The selection of placebo as the comparator is considered the gold standard for medication trials. Eligible participants will be randomized in a 1:1 ratio to tirzepatide or placebo, balancing on site and buprenorphine (BUP) formulation (transmucosal vs extended-release).

Participants will receive tirzepatide or placebo based on randomized assignment, with "dose escalation" of placebo following the schedule for tirzepatide and tirzepatide dosing being consistent with prescribing guidelines. Participants will be administered a subcutaneous (SQ) study medication injection weekly and attend weekly research visits through 26 weeks post-randomization with longer research visits at 1, 3, and 6 months post-randomization. A follow-up visit for final safety measures will be completed at week 30, which takes into account tirzepatide's long half-life.

Duration of participation will be approximately 31 weeks for study participants. Participants will be administered study medication and attend weekly research visits through 6 months post-randomization with longer research visits at 1-, 3-, and 6-months post-randomization. Participants will be provided with a Fitbit to measure sleep. BUP is not a study medication; participants will receive BUP through their clinical provider. A follow-up visit for final safety measures will be completed at week 30.

Enrollment: 310 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Must be ≥18 years of age;
2. Must have moderate to severe OUD;
3. Must, at the time of randomization, be newly initiated on BUP (i.e., within 7 to 28 days) during the current treatment episode, be taking ≥ the recommended target dose for transmucosal BUP57 (or equivalent for extended-release), and have documentation of receiving BUP, including dose and the start date of the current treatment episode, from their BUP provider;
4. Must be willing to be randomized to tirzepatide or placebo and to comply with study procedures, including weekly visits for 6 months;
5. Must be able to understand the study, and having understood, provide written informed consent in English;
6. Must not be breastfeeding; if of child bearing potential, must test negative on the study-administered pregnancy test(s), and if of childbearing potential and engaging /planning to engage in sexual intercourse must agree to effective contraception for the duration of the trial through 30 days after the trial; effective contraception is defined as using: a) birth control injection, an intrauterine device, or implant; or b) two birth control methods - for example birth control pills with a barrier method (e.g., condoms, etc.). o If ever of childbearing potential, a participant is considered to not be of childbearing potential for the study if they are: 1) infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, tubal implants, or tubal ligation), congenital anomaly such as Mullerian agenesis; are 2) post-menopausal defined as ≥ 55 years old not on hormone therapy, who has had at least 12 months of spontaneous amenorrhea; 3) ≥ 55 years old with a diagnosis of menopause prior to starting hormone replacement therapy; or 4) ≥ 40 years old with an intact uterus, not on hormone therapy, who has cessation of menses for at least 1 year without an alternative medical cause, AND a follicle-stimulating hormone ≥ 40 mIU/mL; participants in this category must test negative on the study-administered pregnancy test(s).

Exclusion criteria

1. have a history of type 1 or type 2 diabetes mellitus (other than pregnancy-related diabetes);

2. have a A1C lab result ≥ 6.5%;

3. have a BMI <20.0;

4. have any of the following cardiovascular conditions within 90 days prior to signing consent: acute myocardial infarction, cerebrovascular accident (stroke), unstable angina, or hospitalization due to congestive heart failure (CHF);

5. have a known history of chronic or acute pancreatitis, gallbladder disease, gastroparesis, gastric emptying abnormality, gastroesophageal reflux disease, or other severe gastrointestinal disease;

6. have a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2);

7. have previously taken tirzepatide or have a known history of prior hypersensitivity reaction to any GLP-1 analogue;

8. have renal impairment defined as an estimated glomerular filtration rate (eGFR) value of < 15 mL/min/1.73 m2 or requiring dialysis;

9. have a current, or within the 30 days prior to signing consent, use of, or plan to start during the course of the trial:

   a) medications with glucose lowering properties: GLP-1 analogs, sulfonylurea, insulin, metformin, thiazolidinediones, dipeptidyl peptidase-4 (DPP-IV) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors; b) systemic steroids including prednisone, hydrocortisone, dexamethasone;

10. have a history of suicide attempts in the prior 2 years or significant active suicidal ideation as assessed by a qualified study clinician;

11. have a psychiatric or medical condition that, in the judgment of the site medical clinician (MC), would make study participation unsafe or which would make treatment compliance difficult;

12. have current status as a prisoner OR be currently in jail, prison, or any inpatient overnight facility as required by court of law or have pending legal action or other situation (e.g., unstable living arrangements) that, in the judgement of the site investigator, could prevent participation in the study or in any study activities.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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310 participants in 2 patient groups, including a placebo group

Tirzepatide

Experimental group

Description:

Tirzepatide is available in single dose vials at six doses: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg/0.5 mL. A study MC will administer the once-weekly SQ dose of tirzepatide. Consistent with tirzepatide's prescribing guidelines, participants will be initiated at a once-weekly SQ dose of 2.5 mg/week with a dose increase to 5mg/week at week 5. Consistent with tirzepatide's prescribing information, once the participant has received 5 mg/week for 4 weeks they are eligible for a dose increase if needed.

Treatment:

Drug: Tirzepatide

Placebo

Placebo Comparator group

Description:

A matched placebo (containing saline) will be created for use in the trial. A study MC will administer the once-weekly SQ dose of saline. The process for deciding on "dose increases" will be the same for placebo and tirzepatide

Treatment:

Other: Placebo